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- Presentation
Emerging Oral Therapies for Plaque Psoriasis: New Mechanisms, Efficacy, and Future Treatment Choices
Description
The speaker describes a rapidly changing landscape for oral treatments for plaque psoriasis, emphasizing that oral therapies are beginning to close the efficacy gap with biologics and may be chosen based on patient phenotype and treatment goals. She reviews the current oral options, including ducravacitinib, now FDA-approved for psoriatic arthritis, and a once-daily 75 mg extended-release apremilast option for patients over 50 kg, noting renal limitations. A major focus is icotrokinra, the first oral peptide approved for psoriasis, which blocks the IL-23 receptor through a novel macrocyclic structure and shows strong efficacy in adults, adolescents, and difficult-to-treat high-impact sites such as scalp, genital, hand, and foot disease. The drug demonstrates high rates of clearance, durable 52-week maintenance, and favorable withdrawal data, with safety comparable to placebo and no universal TB testing requirement. She also highlights newer, more refined TYK2 inhibitors, zasocitinib and imvuducitinib, as potent and selective agents with strong PASI responses, good maintenance after withdrawal, and generally acceptable safety aside from some acne or folliculitis signals. Overall, she concludes that innovation is expanding oral psoriasis care from a limited set of choices to a future where treatment selection will be increasingly personalized and strategic.
View moreConclusions
- The field of oral psoriasis treatment appears to be entering a new era in which oral options are increasingly able to approach biologic-like efficacy while improving convenience for patients.
- Deucravacitinib has become a more versatile option because it is now FDA approved for psoriatic arthritis and shows sustained efficacy in that indication.
- The updated once-daily 75 mg extended-release formulation of apremilast improves dosing convenience for eligible adults and pediatric patients, though it is not suitable for severe renal impairment.
- Icotrokinra represents a novel first-in-class oral peptide that blocks the IL-23 receptor and produces strong, durable skin clearance in plaque psoriasis.
- Icotrokinra appears to maintain responses well over time and even after withdrawal, with loss of response occurring gradually rather than immediately.
- Icotrokinra shows particularly strong efficacy and tolerability in adolescents, suggesting that early oral treatment may be especially effective in younger patients.
- Dedicated studies indicate that icotrokinra can also meaningfully improve difficult high-impact sites such as scalp, genital, and some hand/foot psoriasis, although hand/foot disease remains harder to treat.
- The safety profile of icotrokinra was close to placebo in the presented studies, supporting its favorable tolerability.
- Newer TYK2 inhibitors are being refined toward greater potency and selectivity by targeting the JH2 allosteric domain rather than the JH1 active site.
- Zasocitinib and envudeucitinib both demonstrated clinically meaningful and durable efficacy in moderate-to-severe plaque psoriasis with rapid onset and sustained response.
- The newer TYK2 inhibitors were generally well tolerated, with acne or folliculitis emerging as a notable but usually limited adverse effect.
- The overall trajectory of oral psoriasis therapy suggests that treatment selection is increasingly driven by matching drug features to patient phenotype, disease location, age, convenience needs, and desired depth of response rather than by a simple oral-versus-biologic choice.
- Mease P et al. Ann Rheum Dis. 2025;84:84-85.
- Stein Gold et al., EADV 2025, Presentation FC01.
- Gooderham et al., SID 2025, Poster #LB1142.